Since the severity of clinical manifestations of malaria correlates with the presence of tumour necrosis factor a (TNF.alpha.) in the circulation (13,8,15), components of parasitized erythrocytes which induce its production and cause hypoglycaemia (25,6,26) are customarily referred to as toxins (11). The TNF-inducing activity is associated with a phospholipid (3,1).
Endotoxins are responsible for initiation of septic shock which increases the number of fatalities in Gram-negative bacteremia. The mortality from septic shock is high despite advances in antibiotic therapy. Endotoxins are lipopolysaccharides (LPS) which are released from the bacteria and induce shock by stimulating the release of endogenous inflammatory mediators including tumour necrosis factor .alpha. (TNF.alpha.), interleukin 1.beta. (IL-1.beta.), IL-6, IL-8.gamma.-interferon, leukemia inhibitory factor, tissue factor, histamine and nitric oxide. These endogenous mediators act in concert and are either additive or synergistic in their effects. Therefore, therapies designed to inhibit the release or neutralise the activity of single components have shown only modest protection against lethality. LPS interacts with cells by complexing with endotoxin-binding protein and binding CD14, by a pertussis toxin-sensitive p73 receptor, via lectin receptors and by serum-independent hydrophobic mechanisms. The intracellular signalling mechanisms triggered by LPS are not fully elucidated. A therapy which prevents the release of endotoxin from bacteria or was able to neutralise the action of endotoxin before it bound to mammalian cell surfaces would be valuable. At present no effective medicament for either of the above conditions has been developed.